Establishment of Myocardial Regeneration Therapy Using Small Molecule-Responsive Artificial Receptors For Growth Factor Signal Transduction

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Signal transduction from Wnt ligands or Granulocyte Colony Stimulating factor (G-CSF) links to pathways involved in myocardial cell differentiation or cell survival from external stress stimuli. To control these signals in pluripotent stem cells is expected to improve the efficiency for cell survival after implantation as well as for myocardial cell induction. Then, we attempted to generate small molecule-responsive artificial receptors that can activate signal pathways, in the absence of Wnt3a or G-CSF. In the present research project, we constructed chimeric receptors in which single-chain Fv of anti-fluorescein (FL) antibody was tethered to transmembrane/cytoplasmic domains of the receptor for Wnt3a or G-CSF. Mouse ES cells or iPS cells transduced with these chimeric receptors are able to activate the signals in response to FL-conjugated BSA (BSA-FL) as a cognate ligand, and show increased efficiency for myocardial cell differentiation when they are stimulated with BSA-FL.